多柔比星纳米胶束抗肿瘤作用与机制：Pluronic的影响

项目名称： 多柔比星纳米胶束抗肿瘤作用与机制：Pluronic的影响

项目编号： No.81201811

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 沈俐

作者单位： 浙江大学

项目金额： 23万元

中文摘要： 化疗的疗效仍有较大的提升空间。利用纳米载体，改善药物在肿瘤无血管区中的穿透与滞留能力，使药物更容易进入远离微血管的肿瘤细胞；实现化疗药的细胞核DNA靶向；减少或逆转肿瘤多药耐药就可能使目前已有的化疗药发挥更大的抗肿瘤作用。Pluronic是制备纳米胶束的主要材料，其分子量影响纳米胶束的特性。本课题在前期工作基础上，以不同分子量（PEO长度）的Pluronic构建多柔比星纳米胶束，激光共聚焦显微镜和光谱技术从定位定量两方面评价细胞核靶向；采用三维多细胞球体技术和移植瘤模型，研究多柔比星渗入肿瘤实质的深度及瘤内滞留时间；进而评价多柔比星纳米胶束克服多药耐药情况；再从单层细胞培养MTT试验、克隆形成能力、多细胞球体生长与迁移以及对移植瘤的抑制作用等方面研究多柔比星纳米胶束的抗肿瘤效应。本研究从克服多药耐药、改善化疗药的细胞核靶向和瘤内无血管区穿透与滞留能力的角度，探讨提升化疗药抗肿瘤作用的新途径

中文关键词： 阿霉素胶束；普朗尼克；多药耐药；逆转作用；

英文摘要： Due to the toxicity and low efficiency of cytotoxic pharmaceuticals, the therapeutic effect of chemotherapy is still unsatisfied. Using Nanometer carrier, it is possible to improve the efficiency of clinical available cytotoxic pharmaceuticals if the drugs could be delivered to the tumor cells far away from the vessels, then bind to the DNA in the cellular nucleus. It will also be helpful if the nanometer carrier could overcome the multidrug resistance (MDR) to somehow. The molecular weight of Pluronic have great impact on the characteristics of nano-micelles. In this study, based on our former research, doxorubicin-loaded nanomicelles will be prepared using Pluronic of different molecular weights. Cellular nucleus target of the drugs will be studied using Laser confocal scanning microscopy and spectrometry. The penetration and retention of the loaded drugs will be measured via multicellular spheroids and tumor bearing nude mice. Multidrug resistance studies will also be performed. Finally, the anticancer effect of prepared doxorubicin-loaded nanomicelles will be exammed in the levels of monolayer cellular culture, multicellular spheroids model and tumor bearing nude mice. We are investigating a novel route to improve the efficiency of clinical available cytotoxic pharmaceuticals through more efficient tumor pen

英文关键词： Doxorubicin-loaded composite micelles；Pluronic；Multi-drug resistance；Reversal effect；